Oral delivery is considered to be a convenient and widely accepted route of drug administration. Achieving good oral bioavailability for drugs is a cornerstone for an effective oral therapy. The use of an effective carrier for drugs having low bioavailability enables an effective oral administration with improve drug potency and may be used for new drugs, as well as for old medicines that have not historically been available orally.
The term bioavailability with respect to oral administration of drugs is directed to the fraction of drug that has reached the systemic circulation after oral administration, while taking into account both absorption and metabolism of the drug. The bioavailability may be affected/dependent on several factors, some of which are related to the Gastrointestinal (GI) tract and some are related to the metabolism of the drug before entering the systemic circulation. The factors include, for example, such factors as: GI motility, GI pH and enzymatic composition including protease, lipase, nuclease, and the like, Particle (active drug) size, physicochemical interaction with gut content, metabolism of the drug by enzymes and electrolytes in the GI tract, metabolism during the first pass clearance of the drug (such as, for example, metabolism of the drug in the liver), Chemical characteristic of the drug (such as, for example, low lipid solubility, acidity of the drug), and the like.
With respect to protein drugs, two main factors limit their use by oral route of administration. One is the rapid degradation of the protein drugs, which occurs in GI tract by intestinal enzymes and in mucosal tissues that generally cover the body cavities. The other factor that limits the oral administration of protein drugs is that most protein drugs are relatively large molecules and therefore do not easily crosses the intestinal epithelium. As a result, the bioavailability of orally administered protein-based drugs is typically extremely low. Accordingly, the most common route of protein drugs administration is the parenteral route, which has several drawbacks, such as, for example, being inconvenient to the patients, and being more expensive in terms of drug administration. There is therefore an unmet medical need for an effective non-parenteral mode of administration of protein drugs that will provide protection against biological degradation, improve pharmacokinetics and reduce toxicity. Although sophisticated non-parenteral pharmaceutical systems, such as intra-nasal or inhaled systems, have been developed, oral administration is more favorable, having the major advantage of convenience for increased patient compliance. Various strategies for oral administration of protein drugs have been suggested, such as for example in the following publications: U.S. Pat. No. 7,090,868, U.S. Pat. No. 7,195,780, U.S. Pat. No. 7,316,818, WO 06/062544, U.S. Pat. No. 6,071,535, U.S. Pat. No. 5,874,105, U.S. Pat. No. 6,551,576, U.S. Pat. No. 6,808,720, U.S. Pat. No. 7,083,572, US 2007/0184076, WO 06/097793, WO 05/094785, WO 03/066859 and EP0491114B1.
Additionally, since bioavailability may be low for non-protein drugs there is also a growing need for the development of a drug delivery system that can protect the drug from the environment and may direct the drug to a targeted site or organ, obviating unwanted side effects while simultaneously reducing dose and toxicity, improve potency of the drug, and improve the drug's bioavailability.